Melanin is the primary cause of skin colorations in mammals, particularly humans. Broadly speaking, this pigment provides a number of beneficial characteristics to humans, most notably, perhaps, the ability to protect from Ultraviolet-B (UV-B) radiation (commonly associated with exposure to sun rays or in tanning beds). Such a compound is naturally produced within the skin, through melanogenesis within melanocytes at the base of the epidermis. The amino acid tyrosine is the base source of such a pigment (as well as a number of other important compounds within the body, including adrenaline), reacting with tyrosinase to initially form Dopa and Dopaquinone. This converted base compound then either reacts with cysteine to form pheomelanins, which contribute to pink and red colorations within a person's hair and skin, or converts further to leucodopachrome and ultimately to a generally accepted polymer of 5,6-dihydroxyindole (or like structures) to form eumelanins, the dark-colored pigments that are most prevalent within skin and hair. These reactions ultimately occur in relation to melanosomes present in the epidermis of the skin, and are transferred via dendritic formations from the melanocytes themselves to keratinocytes located within the outer skin layers (as well as the hair follicles and hairs, too). Although the complexities of such melanin compound formation are far more in-depth than summarized above, such pathways are typically and generally understood as the basis of such pigment generation via natural routes.
As important as such pigments are to human development and skin protection, the potential for uncontrolled melanin generation and transfer to keratinocytes, particularly in localized and/or clustered areas of a person's skin, has proven to cause certain undesirable and potentially harmful effects. For instance, hyperpigmentation of the skin has proven to be problematic on a number of levels, dependent largely upon the individual involved. For instance, uneven skin tone and localized dark coloration blemishes contribute to cosmetic difficulties. Likewise, other troubling conditions associated with hyperpigmentation may occur, including Celiac Disease, Grave's Disease, and Addison's Disease, to name but a few. In essence, the overabundance of melanin build up within concentrated skin regions is undesirable and potentially harmful to humans, necessitating investigations into possible remedies that allow for safe and reliable skin brightening/lightening effects.
Generally, however, such treatments for hyperpigmentation have proven rather elusive, at least in terms of effectiveness and overall acceptance for safety. As noted above, such a dark pigment is derived through some rather complicated in situ reactions from the amino acid Tyrosine. The ability to control such a reaction, particularly in terms of final melanin synthesis, has thus led to centered developments at certain points in the pigment creation pathway. Most notably is the initial conversion of Tyrosine to Dopa and then Dopaquinone. Again, as alluded to above, Tyrosinase is required to convert the initial Tyrosine amino acid to Dopa, as well as the further conversion thereof to Dopaquinone. As such, many skin brightening compositions and methods solely concern the deactivation or otherwise reduction of efficacy of such an enzyme in order to prevent such conversions in the first place. The problems with these past attempts at skin brightening through this limited method are primarily the reliance upon individual compounds that function to reduce Tyrosinase generation, presence, and/or activity to attain such a result. The most common individual compounds utilized for this purpose have been hydroquinone, kojic acid, and arbutin. Hydroquinone, unfortunately, has been considered a potential carcinogen, particularly in large doses (e.g., greater than 5% by weight of an applied formulation), as well as a skin irritant that creates more problems than it solves (particularly in terms of cytotoxicity). This compound also exhibits a significant rate of oxidation upon exposure to the environment (air and light, for instance), thus lowering efficacy, not to mention upon exposure to Tyrosinase itself (thus requiring exactness in terms of actual proportions present to accord any degree of effectiveness at deactivating the enzyme). Arbutin is a glycosylated hydroquinone that exhibits similar effects as hydroquinone itself, and is particularly susceptible to reactions that remove the glycoside function on the base compound, thus rendering the same basic compound known for carcinogenicity. Kojic acid, on its own, is rather limited in its effects with Tyrosinase activity, particularly due to low bioavailability and resultant low efficacy.
In any event, the ability to inhibit production of Tyrosinase within the body (or, again, causing deactivation thereof within the body) may allow for melanin production at a reduced rate. Skin brightening is thus possible through the inclusion of acceptable levels of such Tyrosinase inhibitors within skin application formulations. Coupled with a compound (or compounds) that aids in removing epidermal layers (particularly if the most trouble melanin production locations are in those layers), the potential to effectuate melanin-containing epidermis layer removal and simultaneous prevention of further melanin production may result in favorable results in this manner. Again, however, the main deficiencies of the formulations currently available for such a purpose are the utilization of hydroquinone as typical main ingredient, and the lack of a suitable epidermis removal compound that does not protect from the irritating effects of the hydroquinone compound on and within such exposed epidermis layers.
There thus remains a need for an acceptable and effective method of providing melanin removal from dermal layers and/or reduction in melanin production capability within the body itself. Such a method and formulation would preferably utilize more than just tyrosinase inhibition as the means for such an end result, primarily due to the necessity for undesirable amounts of suspect and/or ineffective compounds to that end. As well, the utilization of retinol or like product on its own for skin layer removal purposes is frowned upon due to long-term harmful effects associated with such an action and potential scarring results as well. Thus, the introduction and undertaking of other pathways in addition to those noted above would be of significant interest, particularly if the results provided not only the beneficial melanin reduction, etc., within a target patient's skin layers, but also other results such as skin scar repair and softening, at least. The ability to impart such effects with formulations that are not only free from known carcinogens, but also free from compounds that may be potentially harmful to pregnant and/or nursing women (since significant and unwanted melanin colorations are associated with pregnancy and childbirth), would be a noticeable and invited improvement in this art as well. To date, however, such a new development in this area has yet to be provided.